Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring最新文献

{"title":"Real-world implementation of lecanemab in Alzheimer's disease: A Japanese cohort.","authors":"Sho Shimohama, Shogyoku Bun, Ryo Shikimoto, Hiroi Tomioka, Toshiki Takayama, Yu Mimura, Hiroki Sasaguri, Koji Sekiguchi, Yoshinori Nishimoto, Yu Iwabuchi, Hajime Tabuchi, Jin Nakahara, Masaru Mimura, Daisuke Ito","doi":"10.1002/dad2.70492","DOIUrl":"10.1002/dad2.70492","url":null,"abstract":"<p><strong>Introduction: </strong>Real-world evidence for lecanemab remains limited, particularly among Asian populations. We evaluated the feasibility, safety, biomarker profiles, and short-term clinical outcomes of lecanemab in practice in Japan.</p><p><strong>Methods: </strong>We screened 321 patients with early Alzheimer's disease (AD) and confirmed amyloid pathology using amyloid positron emission tomography (PET) or cerebrospinal fluid analysis. Plasma amyloid-β42/40 was assessed when available. Among these, 102 initiated lecanemab and underwent structured magnetic resonance imaging (MRI) surveillance with 6 months of follow-up.</p><p><strong>Results: </strong>Most treated patients had a Clinical Dementia Rating-Global (CDR-Global) score of 0.5 (96.1%), and 6-month treatment persistence exceeded 85%. Amyloid-related imaging abnormalities (ARIA), predominantly mild and asymptomatic ARIA-H, occurred in 11.4%, whereas no cases of isolated ARIA with effusion or edema (ARIA-E) were observed. One macrohemorrhagic and two moderate-severe radiographic ARIA with hemorrhage or hemosiderin deposition (ARIA-H) developed, which led to discontinuation of the treatment. Cognitive and functional measures remained generally stable over 6 months, with changes comparable to those reported in the phase 3 CLARITY-AD trial. Plasma-PET discordance highlighted the complementary value of multimodal biomarker interpretation.</p><p><strong>Discussion: </strong>Lecanemab was feasible and generally well tolerated under structured MRI monitoring in routine Japanese practice.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"18 3","pages":"e70492"},"PeriodicalIF":4.4,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13613027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149065771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracerebral microvascular burden links to dementia risk and brain structural changes: Evidence from a large-scale cohort study.","authors":"Jialin Li, Yingzhe Wang, Chunyu Yin, Mei Cui, Jincheng Li, Chen Suo, Kelin Xu, Zhenqiu Liu, Li Jin, Xingdong Chen, Yanfeng Jiang","doi":"10.1002/dad2.70489","DOIUrl":"10.1002/dad2.70489","url":null,"abstract":"<p><strong>Introduction: </strong>The contribution of extracerebral microvascular disease (MVD) burden to dementia risk remains unclear.</p><p><strong>Methods: </strong>Among 484,896 UK Biobank participants (median follow-up 8.5 years), baseline extracerebral MVD (retinopathy, nephropathy, peripheral neuropathy) and incident dementia were identified via hospital records. Aging-related brain changes were evaluated using magnetic resonance imaging (MRI) -derived volumes and white matter integrity.</p><p><strong>Results: </strong>MVD was 2.6 times more prevalent among participants who developed dementia than dementia-free individuals (8.0% vs 3.1%) and ranked second among vascular comorbidities after coronary artery disease. Each additional MVD burden was associated with a higher dementia risk, comparable to coronary artery disease (hazard ratio = 1.69 vs. 1.72). Earlier onset conferred stronger risk, and coexisting vascular diseases further amplified associations (<i>p</i>-trend < 0.001). MVD burden was also associated with global brain atrophy and reduced white matter integrity.</p><p><strong>Discussion: </strong>Extracerebral MVD burden is associated with dementia risks and brain imaging changes, supporting integrated vascular risk stratification and management for dementia.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"18 3","pages":"e70489"},"PeriodicalIF":4.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149041879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive evaluation of AT(N) imaging biomarkers for predicting cognitive decline.","authors":"Tom Earnest, Braden Yang, Deydeep Kothapalli, Aristeidis Sotiras","doi":"10.1002/dad2.70480","DOIUrl":"10.1002/dad2.70480","url":null,"abstract":"<p><strong>Introduction: </strong>Few studies have investigated how different Alzheimer's disease biomarker definitions affect predictions of cognitive decline.</p><p><strong>Methods: </strong>We predicted cognitive decline using 42 biomarker definitions spanning amyloid beta, tau, and neurodegeneration in 383 ADNI participants with baseline neuroimaging and longitudinal cognitive assessments. We identified optimal predictors for each pathology and variable type (continuous, binary, non-binary categorical) using nested cross-validation. Models were compared against support vector machines (SVMs) incorporating brain-wide pathology. In a subsample, we compared imaging-based biomarkers with biofluids (cerebrospinal fluid and plasma).</p><p><strong>Results: </strong>We observed substantial variability in accuracy, even for measures of the same pathology. Tau biomarkers were most accurate, performing comparably to models incorporating all three pathologies. Binarization of biomarkers mostly preserved accuracy, while SVMs trained on brain-wide pathology data generally did not improve performance. Imaging-based biomarkers consistently outperformed biofluid ones.</p><p><strong>Discussion: </strong>Imaging-based biomarker definitions are not interchangeable and can influence the assessment of cognitive decline.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"18 3","pages":"e70480"},"PeriodicalIF":4.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149041873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world utility of plasma GFAP and NfL in early-onset AD and FTD.","authors":"Pratishtha Chatterjee, Svetlana Ivanic, Adam Southon, Claire McCarthy, Sheila K Patel, Maja Christensen, David Darby, Ashley I Bush, Scott Ayton, Michelle M Mielke, Emilio Werden, Amy Brodtmann","doi":"10.1002/dad2.70490","DOIUrl":"10.1002/dad2.70490","url":null,"abstract":"<p><strong>Introduction: </strong>Plasma glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are promising blood biomarkers, but their real-world diagnostic utility in early-onset dementia is understudied.</p><p><strong>Methods: </strong>Plasma GFAP, NfL, and phosphorylated tau (p-tau)217 were measured using Simoa in 118 patients with cognitive complaints, clinically classified as non-neurodegenerative conditions (non-ND; <i>n</i> = 52), early-onset Alzheimer's disease (EOAD; <i>n</i> = 39), frontotemporal dementia (FTD; <i>n</i> = 20), or other-neurodegenerative dementia (ND)/ dementia (<i>n</i> = 7). P-tau217 defined Alzheimer's disease pathology.</p><p><strong>Results: </strong>GFAP was elevated in EOAD compared to non-ND, FTD, and other-ND, and distinguished EOAD from non-ND (area under the curve [95% confidence interval (CI)]: 0.924 [0.871-0.977]) but performed poorly for FTD versus non-ND (0.636 [0.496-0.775]). NfL was most elevated in FTD and EOAD, distinguishing both (FTD: 0.869 [0.778-0.961]; EOAD: 0.770 [0.673-0.867]) from non-ND, but less effective for FTD versus EOAD (0.750 [0.597-0.903]). GFAP appeared stable in severe renal impairment, while NfL increased.</p><p><strong>Discussion: </strong>These findings support integrating GFAP and NfL into clinical dementia assessments, with GFAP offering added diagnostic specificity in cases of severe renal impairment; however, validation in larger cohorts is needed.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"18 3","pages":"e70490"},"PeriodicalIF":4.4,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13593584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149026764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A scalable workflow using digital cognitive assessment and pTau217 for MCI detection.","authors":"Srinivasan Vairavan, Nicholas Griffin, David Wilson, Gallen Triana-Baltzer, Victoria Brugada-Ramentol, Elena Vera-Campuzano, Daniel Alcolea, Silvia Fallone, Lucy Mackintosh, Lindsey Mette, James D Doecke, Joanne Robertson, Larry Ward, Gonzalo Sánchez Benavides, Carolina Minguillon, Clàudia Porta Mas, Adrià Tort-Merino, Mircea Balasa, Oriol Grau Rivera, Marc Suárez Calvet, Lewis Taylor, Íñigo Rodríguez-Baz, Javier Arranz, Juan Fortea, Ioannis Tarnanas, Marc Jones, Gayle Wittenberg, Emmanuel Streel, Maria Florencia Iulita","doi":"10.1002/dad2.70486","DOIUrl":"10.1002/dad2.70486","url":null,"abstract":"<p><strong>Introduction: </strong>Blood biomarkers like phosphorylated tau (p-tau)217 offer high diagnostic accuracy for Alzheimer's disease (AD) but face implementation challenges in low-prevalence settings. We evaluated the Altoida NeuroMarker Platform as a digital cognitive triage tool before plasma p-tau217 testing.</p><p><strong>Methods: </strong>XGBoost models were trained to predict mild cognitive impairment (MCI) and p-tau217 status in 688 individuals across Australia, Spain, and the United States using the Altoida NeuroMarker. p-tau217 status was dichotomized using a threshold of 0.04 pg/mL (LucentAD). We modeled a two-step workflow (Altoida, plasma p-tau217) to enrich downstream biomarker testing, assuming 30% prevalence of AD pathology.</p><p><strong>Results: </strong>The Altoida NeuroMarker accurately identified MCI (receiver operating characteristic area under the curve [ROC AUC] = 0.89 ± 0.01) and p-tau217 elevation (ROC AUC = 0.77 ± 0.08). Predicted MCI was significantly associated with elevated pTau217 (<i>p</i> = 0.004). When used upstream, the Altoida NeuroMarker ruled out 64.4% of participants (negative predictive value 90.2%), shifting the pre-test probability of AD pathology to 66.6%, and improving the modeled positive predictive value of plasma p-tau217 from 81.7% to 95.3%.</p><p><strong>Discussion: </strong>This workflow outlines a scalable path to enrich blood-based biomarker testing after digital cognitive screening.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"18 3","pages":"e70486"},"PeriodicalIF":4.4,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13584318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148992443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Individualized cholinergic pathway degeneration in Alzheimer's disease characterized by normative modeling.","authors":"Shuoyun Feng, Huixiang Zhuang, Chang Xu, Xinyu Guo, Li Cao, Yaou Liu, Yue Guan, Yao Li","doi":"10.1002/dad2.70485","DOIUrl":"10.1002/dad2.70485","url":null,"abstract":"<p><strong>Introduction: </strong>Cholinergic pathway degeneration is implicated in Alzheimer's disease (AD), but its individualized characterization in AD and mild cognitive impairment (MCI) remains limited.</p><p><strong>Methods: </strong>We constructed lifespan normative models of medial and lateral cholinergic pathways using >6000 diffusion MRI scans from healthy individuals. These models were applied to 1742 scans from 725 participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Individualized diffusion abnormalities were integrated into a composite cholinergic pathway degeneration index (CPDI). Group differences and longitudinal associations with cognitive decline and progression were evaluated.</p><p><strong>Results: </strong>CPDI was higher in MCI and AD participants than in controls, and increased longitudinally in patients with AD and in patients with MCI who progressed to AD. Higher baseline CPDI was associated with an increased risk of progression from MCI to AD and faster decline in global cognition, memory, language, and executive function.</p><p><strong>Discussion: </strong>CPDI provides an individualized biomarker of cholinergic pathway degeneration with prognostic relevance in AD.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"18 3","pages":"e70485"},"PeriodicalIF":4.4,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13583057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148992450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time to diagnosis in FTLD-associated syndromes in Latin America.","authors":"Nahuel Magrath-Guimet, Florentina Morello-Garcia, Loana De Los Santos, Carolina Ardohain-Cristalli, Eugenia Tabernero, Hernán Chaves, Pablo Bagnati, Ricardo Francisco Allegri, Joaquin Migeot, Juliana Acosta-Uribe, Isabel Elaine Allen, David Aguillon, Jose Alberto Avila-Funes, Maria Isabel Behrens, Martin Bruno, Luis Ignacio Brusco, Nilton Custodio, Elisa de Paula França Resende, Claudia Duran Aniotz, Marilu Gorno-Tempini, Agustin Ibanez, Kenneth S Kosik, Marcelo Adrian Maito, Diana Matallana, Bruce Miller, Mike Nalls, Stefanie D Piña-Escudero, Kate Possin, Guido Rocatti, Hernando Santamaria-Garcia, Andrea Slachevsky, Ana Luisa Sosa, Leonel Takada, Jared W Taylor, Lina M Zapata-Restrepo, Jennifer S Yokoyama, Victor Valcour","doi":"10.1002/dad2.70476","DOIUrl":"10.1002/dad2.70476","url":null,"abstract":"<p><strong>Introduction: </strong>Frontotemporal lobar degeneration (FTLD) often affects younger patients, making time to diagnosis especially consequential. Most evidence comes from high-income countries, with limited data from Latin America.</p><p><strong>Methods: </strong>We studied 415 individuals with FTLD-associated syndromes from 12 sites in six Latin American countries in the Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat) cohort. Time to diagnosis was calculated using clinician-reported symptom onset (T-Reported) and criteria-based onset (T-Criteria). Associations with phenotype, social determinants of health, education, age at onset, sex, symptom presentation, and genetic status were examined.</p><p><strong>Results: </strong>Mean time to diagnosis was 3.33 years using T-Reported and 2.97 years using T-Criteria. Times were longest in behavioral variant frontotemporal dementia and primary progressive aphasia variants. Younger age at onset was associated with longer time to diagnosis. Genetic carriers showed earlier onset but similar time to diagnosis.</p><p><strong>Discussion: </strong>Time to diagnosis remains substantial, particularly in younger patients and canonical frontotemporal dementia phenotypes.</p><p><p>Mean time to diagnosis remains high across frontotemporal lobar degeneration (FTLD) syndromes.Diagnostic delay in FTLD in Latin America averages ≈3 years.Younger onset is linked to longer time to diagnosis.Canonical frontotemporal dementia phenotypes show the longest diagnostic delays.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"18 3","pages":"e70476"},"PeriodicalIF":4.4,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13575979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imaging for anti-amyloid therapy eligibility: Comparing GRE and SWI in detecting microhemorrhages and superficial siderosis.","authors":"Jeremy N Ford, Suely Fazio Ferraciolli, Odette Ganem Chagui, Marvin Relerford, Esteban Calle Cadavid, John Dickson, Maryam Vejdani-Jahromi, Matthew N DeSalvo, Liliana A Ramirez Gomez, Seonghwan Yee, Harry R Griffin, Benjamin Kozak, Saurabh Rohatgi, Raymond Y Huang, Teresa Gomez-Isla, Javier Romero","doi":"10.1002/dad2.70477","DOIUrl":"10.1002/dad2.70477","url":null,"abstract":"<p><strong>Introduction: </strong>Anti-amyloid therapies such as lecanemab require magnetic resonance imaging (MRI) screening to exclude patients with > 4 gradient-recalled echo (GRE)-detected microhemorrhages or any superficial siderosis (SS). Although GRE and susceptibility-weighted imaging (SWI) are both accepted, they differ in detection performance.</p><p><strong>Methods: </strong>We retrospectively analyzed 224 eligibility MRIs with paired GRE and SWI from a single academic health system. Six neuroradiologists assessed a 20-scan reliability subset; the remaining 204 scans were assigned to one rater for hemorrhagic lesion detection and MRI-based eligibility classification. Interobserver reliability was calculated using intraclass correlation coefficients (ICCs), and sequence differences were evaluated using non-parametric tests.</p><p><strong>Results: </strong>SWI detected more microhemorrhages than GRE (mean 1.24 vs. 0.67, <i>p <</i> 0.0001), identified eight additional SS cases, and showed higher interobserver agreement (ICC 0.951 vs. 0.764, <i>p <</i> 0.01). SWI classified more patients as MRI ineligible than GRE (26/204 [12.7%] vs. 11/204 [5.4%]).</p><p><strong>Discussion: </strong>SWI identifies more exclusionary hemorrhagic findings and demonstrates greater reproducibility than GRE.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"18 3","pages":"e70477"},"PeriodicalIF":4.4,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13575324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"P-tau181 is longitudinally associated with a proxy measure of mild behavioral impairment among frail older adults: Insights from COGFRAIL.","authors":"Federico Bellelli, Emmanuel González, Alberta Peluso, Davide Angioni, Sandrine Sourdet, Maria Soto Martin","doi":"10.1002/dad2.70392","DOIUrl":"10.1002/dad2.70392","url":null,"abstract":"<p><strong>Introduction: </strong>Cross-sectional studies link Alzheimer's disease (AD) pathogenesis to mild behavioral impairment (MBI), but longitudinal evidence remains limited. We examined whether plasma phosphorylated tau (p-tau)181 predicts progression of an MBI-proxy over 2 years in pre-frail and frail older adults with mild cognitive impairment.</p><p><strong>Methods: </strong>This is a secondary analysis of the Cognitive Function and Prevalence of Amyloid Marker in Frail Older Adults study, including 174 participants (mean age = 82.9 ± 5.4 years). Plasma p-tau181 was analyzed both as a continuous variable and by tertiles. MBI was approximated using a Neuropsychiatric Inventory Questionnaire (NPI-Q)-based algorithm.</p><p><strong>Results: </strong>Participants in the highest tertile showed greater progression in the number of affected NPI-Q-derived MBI domains and overall severity compared to the lowest tertile. Continuous analyses showed a similar but non-significant trend (<i>P</i> = 0.08).</p><p><strong>Discussion: </strong>Amyloid and tau pathology may contribute not only to cognitive but also to behavioral impairment, supporting the hypothesis that MBI reflects underlying AD pathology, and may help identify individuals at higher risk of neuropsychiatric progression.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"18 3","pages":"e70392"},"PeriodicalIF":4.4,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13575329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linking cognitive variability and Alzheimer's disease biomarkers by neurocognitive status.","authors":"Shayne S-H Lin, Alicia Milam, Andrew M Kiselica, Stephen L Aita, Mubarick Saeed, Troy Webber, Steven Paul Woods, Nicholas C Borgogna, Keenan A Walker, Vidyulata Kamath, Kristina Visscher, Charles F Murchison, David S Geldmacher, Erik D Roberson, Benjamin D Hill, Victor A Del Bene","doi":"10.1002/dad2.70481","DOIUrl":"10.1002/dad2.70481","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to assess intra-individual cognitive variability (IICV) in relation to Alzheimer's disease (AD) biomarkers.</p><p><strong>Methods: </strong>The National Alzheimer's Coordinating Center sample (<i>n</i> = 879), aged 50+ with a complete neuropsychological evaluation and AD biomarker data available (64% cognitively intact; 36% cognitively impaired). Moderated regression models using AD biomarkers, neurocognitive status, and interaction effects predicted IICV. AD biomarkers included cerebrospinal fluid (CSF) measures of Aβ_1-42, phosphorylated tau 181 (p-Tau₁₈₁), total tau (t-Tau), and amyloid positron emission tomography.</p><p><strong>Results: </strong>Increased AD biomarker burden was associated with increased IICV among cognitively impaired individuals (correlational strength ranging from 0.149 to 0.460) but not among the cognitively intact group.</p><p><strong>Discussion: </strong>Increases in measures of amyloid, soluble tau, and neurodegeneration are associated with increased IICV among cognitively impaired older adults. The findings underscore the potential of IICV as a sensitive outcome measure. Future studies should replicate findings longitudinally and in more diverse samples.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"18 3","pages":"e70481"},"PeriodicalIF":4.4,"publicationDate":"2026-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13572577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148972411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}